3 years ago

Pulmonary vasodilation by phosphodiesterase 5-inhibition is enhanced and nitric oxide-independent in early pulmonary hypertension after myocardial infarction.

Merkus, Duncker, Houweling, van Duin, Uitterdijk
Myocardial infarction (MI) may result in pulmonary hypertension (PH). Inhibition of phosphodiesterase 5 (PDE5), the enzyme responsible for the breakdown of cGMP in vascular smooth muscle, has become part of the contemporary therapeutic armamentarium for pulmonary arterial hypertension and may also be of benefit in PH secondary to MI. Nitric oxide (NO) is an important source of cGMP and can be enhanced in early PH and decreased in severe PH. In the present study we investigated if PDE5-inhibition ameliorates pulmonary hemodynamics in swine with PH secondary to MI and whether NO is essential. The PDE5-inhibitor EMD360527 was administered in awake chronically instrumented swine with and without MI. At rest, PDE5-inhibition produced pulmonary vasodilation as evidenced by decrease in pulmonary vascular resistance, which was more pronounced in MI (n=5) compared to normal swine (n=10; P<0.01) and was accompanied by an increase in stroke volume in MI swine. Both pulmonary vasodilation and increased stroke volume were maintained during exercise, suggesting that this therapy may improve exercise capacity in patients with PH secondary to MI. Interestingly, prior inhibition of NO significantly enhanced (P<0.01) pulmonary vasodilation by PDE5-inhibition in both normal (n=8) and MI swine (n=5; P<0.05 vs normal). These observations suggest that the increased vasodilator responses to PDE5-inhibition after MI were not due to an increase in NO-mediated cGMP production. These observations indicate that PDE5-inhibition represents an interesting pharmacotherapeutic approach in early PH following a recent MI, to prevent overt PH.

Publisher URL: http://doi.org/10.1152/ajpheart.00370.2017

DOI: 10.1152/ajpheart.00370.2017

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